Primary objectives of this project are to uncover and delineate naturally occurring delayed-type iso-hypersensitivities (DIH) towards heritable iso- antigens, to determine the function of this type phenomenon, and to seek adverse or beneficial conditions controlled by DIH. Thus far, we have described two instances of such iso-reactivity. The first, in guinea pigs, can be detected in vivo by eliciting delayed dermal reactions to an iso-antigenic serum factor (SF) and in vitro by inhibiting macrophage migration with SF as well as by lymphocyte blastogenesis that is triggered by SF. The second, described with M. Howe and A. Goldstein in mice, is revealed by neonatal T cells replicating in the presence of mitomycin-treated, isogenic, adult spleen cells. We continue investigations in these areas with special attention upon iso- geneic lymphocyte interactions. Another objective is to ascertain in what ways the spleen determines immunocompetence. We have learned that hereditarily spleenless mice synthesize depressed amounts of IgM and perhaps one variety of IgG. In addition, bone marrow and thymic cells transplanted from mice lacking spleens from birth were incapable of cooperating in IgM and IgG responses to sheep erythrocytes. Our new studies center upon the effects that presence and absence of the spleen may have on differentiation of precursor lymphoid cells. A further objective has been to investigate the effects dextran, a common blood expander, has upon immunological responses that are evoked by other unrelated antigens. We have reported that its administration to guinea pigs and mice markedly changes responses to antigens such as sheep erythrocytes or bovine gamma globulin and to a hapten, picryl chloride. Humoral antibodies and delayed hypersensitivity can be heightened and depressed depending on when dextran is given relative to antigen. We are pursuing this work from the viewpoints of (a) understanding initiation and prevention of immune responses as well as, (b) learning about the shifts in synthesis of immunoglobulins M and G.